Concurrent use of terfenadine and ketoconazole triggers life-threatening torsades de pointes due to inhibition of terfenadine metabolism.
Does concurrent use of terfenadine and ketoconazole increase the risk of torsades de pointes?
Highlights the critical importance of recognizing drug-drug interactions, specifically the inhibition of oxidative metabolism, in preventing life-threatening arrhythmias like torsades de pointes.
In 1989, the occurrence of a rare, life-threatening ventricular arrhythmia (torsades de pointes) in an otherwise healthy young woman led alert clinicians at the Naval Hospital in Bethesda, Md, to consider the possibility that the patient's near-fatal arrhythmia was triggered by a drug-drug interaction involving her antihistamine (terfenadine) and her antifungal (ketoconazole) medications.1Consulting clinical pharmacologists from the Uniformed Services University of the Health Sciences and the US Food and Drug Administration (FDA) suggested that ketoconazole inhibited the oxidative metabolism of terfenadine. Analysis of blood samples revealed that the patient had high levels of unmetabolized terfenadine, a compound not usually detectable in blood because it is metabolized so quickly. Review of reports to the FDA's spontaneous reporting system revealed that among additional cases of torsades de pointes in patients receiving terfenadine, many were also receiving ketoconazole. This evidence led the FDA to ask Marion Merrill Dow, Kansas City, Mo,
Carl C. Peck (Wed,) conducted a editorial in Torsades de pointes. Concurrent terfenadine and ketoconazole was evaluated. Concurrent use of terfenadine and ketoconazole triggers life-threatening torsades de pointes due to inhibition of terfenadine metabolism.
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